scholarly journals Circulating Tumour DNAs and Non-Coding RNAs as Liquid Biopsies for the Management of Colorectal Cancer Patients

2020 ◽  
Vol 2 (3) ◽  
pp. 212-235
Author(s):  
Andrea Lampis ◽  
Michele Ghidini ◽  
Margherita Ratti ◽  
Milko B. Mirchev ◽  
Ali Fuat Okuducu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Predictive Biomarkers ◽  
Minimal Invasive ◽  
Response To Therapy ◽  
Precision Oncology ◽  
Liquid Biopsies ◽  
Tumour Formation ◽  
Non Coding Rnas ◽  
Metastatic Sites ◽  
Colorectal Cancer Patients

Circulating tumour DNAs and non-coding RNAs present in body fluids have been under investigation as tools for cancer diagnosis, disease monitoring, and prognosis for many years. These so-called liquid biopsies offer the opportunity to obtain information about the molecular make-up of a cancer in a minimal invasive way and offer the possibility to implement theranostics for precision oncology. Furthermore, liquid biopsies could overcome the limitations of tissue biopsies in capturing the complexity of tumour heterogeneity within the primary cancer and among different metastatic sites. Liquid biopsies may also be implemented to detect early tumour formation or to monitor cancer relapse of response to therapy with greater sensitivity compared with the currently available protein-based blood biomarkers. Most colorectal cancers are often diagnosed at late stages and have a high mortality rate. Hence, biomolecules as nucleic acids present in liquid biopsies might have prognostic potential and could serve as predictive biomarkers for chemotherapeutic regimens. This review will focus on the role of circulating tumour DNAs and non-coding RNAs as diagnostic, prognostic, and predictive biomarkers in the context of colorectal cancer.

scholarly journals Facile profiling of molecular heterogeneity by microfluidic digital melt

2018 ◽  
Vol 4 (9) ◽  
pp. eaat6459 ◽  
Author(s):  
Christine M. O’Keefe ◽  
Thomas R. Pisanic ◽  
Helena Zec ◽  
Michael J. Overman ◽  
James G. Herman ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Single Molecule ◽  
Rapid Assessment ◽  
Suppressor Gene ◽  
Molecular Heterogeneity ◽  
Liquid Biopsies ◽  
Digital Microfluidic ◽  
Colorectal Cancer Patients

This work presents a digital microfluidic platform called HYPER-Melt (high-density profiling and enumeration by melt) for highly parallelized copy-by-copy DNA molecular profiling. HYPER-Melt provides a facile means of detecting and assessing sequence variations of thousands of individual DNA molecules through digitization in a nanowell microchip array, allowing amplification and interrogation of individual template molecules by detecting HRM fluorescence changes due to sequence-dependent denaturation. As a model application, HYPER-Melt is used here for the detection and assessment of intermolecular heterogeneity of DNA methylation within the promoters of classical tumor suppressor genes. The capabilities of this platform are validated through serial dilutions of mixed epialleles, with demonstrated detection limits as low as 1 methylated variant in 2 million unmethylated templates (0.00005%) of a classic tumor suppressor gene,CDKN2A(p14ARF). The clinical potential of the platform is demonstrated using a digital assay forNDRG4, a tumor suppressor gene that is commonly methylated in colorectal cancer, in liquid biopsies of healthy and colorectal cancer patients. Overall, the platform provides the depth of information, simplicity of use, and single-molecule sensitivity necessary for rapid assessment of intermolecular variation contributing to genetic and epigenetic heterogeneity for challenging applications in embryogenesis, carcinogenesis, and rare biomarker detection.

scholarly journals Molecular Targets for the Treatment of Metastatic Colorectal Cancer

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2350
Author(s):  
Romain Cohen ◽  
Thomas Pudlarz ◽  
Jean-François Delattre ◽  
Raphaël Colle ◽  
Thierry André
Keyword(s):  
Colorectal Cancer ◽  
Molecular Targets ◽  
Predictive Biomarkers ◽  
Therapeutic Strategies ◽  
Her2 Amplification ◽  
Liquid Biopsies ◽  
Braf Mutations ◽  
Genetic Characteristics ◽  
New Developments ◽  
The Past

Over the past years, colorectal cancer (CRC) was subtyped according to its molecular and genetic characteristics, allowing the development of therapeutic strategies, based on predictive biomarkers. Biomarkers such as microsatellite instability (MSI), RAS and BRAF mutations, HER2 amplification or NTRK fusions represent major tools for personalized therapeutic strategies. Moreover, the routine implementation of molecular predictive tests provides new perspectives and challenges for the therapeutic management of CRC patients, such as liquid biopsies and the reintroduction of anti-EGFR monoclonal antibodies. In this review, we summarize the current landscape of targeted therapies for metastatic CRC patients, with a focus on new developments for EGFR blockade and emerging biomarkers (MSI, HER2, NTRK).

Predictive markers for the treatment of colorectal cancer with cetuximab

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13500-13500 ◽  
Author(s):  
E. Razis ◽  
E. Briasoulis ◽  
I. Kostopoulos ◽  
M. Bobos ◽  
C. Christodoulou ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Single Agent ◽  
Skin Toxicity ◽  
Complete Response ◽  
Response To Therapy ◽  
Egfr Expression ◽  
Gene Status ◽  
Line Of Therapy ◽  
Colorectal Cancer Patients ◽  
Line P

13500 Background: Cetuximab is an anti-EGFR monoclonal antibody with activity in colorectal cancer. Patients most likely to benefit should be identified using molecular markers. Methods: A retrospective analysis was performed on patients treated with cetuximab who had paraffin embedded tissue available for testing. Tumor specimens were tested for EGFR (31G7, Zymed), PTEN (28H6, Novocastra) and pAkt 1/2/3 (Thr 308, Santa Cruz) expression by IHC. The EGFR gene status was investigated by FISH (Vysis). Results: Seventy-two patients were identified. EGFR expression was detected in 32/68 patients tested. PTEN was positive in all cases tested (64/64) and pAkt in 52 of 64 patients, in >70% of cells in 21/64 cases. Most patients were treated with cetuximab in various combinations, three patients received it as a single agent and 7 patients in more than one line of therapy. Median follow-up from diagnosis was 30.7 months and from Cetuximab initiation 6.9 months. Median survival from diagnosis has not been reached yet but from initiation of Cetuximab it is 13.6 months. 19 patients achieved a PR and 1 a CR. Most patients with PR were treated in first or second line however, 6 patients achieved a PR in 3rd line and 3 in subsequent lines. The patient with complete response, was treated in first line with CPT 11 and Cetuximab. TTP was 7.4 months for patients treated with Cetuximab in 1st line, 7.5 in 2nd line and 5.3 in 3rd line. Survival did not correlate significantly with any of the immunohistochemically assessed parameters. TTP correlated significantly with pAkt overexpression for patients treated in 3rd line (p=0.0065). The CR was seen in the only patient with EGFR amplification.The presence of skin toxicity did not correlate with response to therapy. Conclusions: Overexpression of pAkt may correlate with response to Cetuximab in colorectal cancer. No significant financial relationships to disclose.

Thrombotic events in metastatic colorectal cancer patients treated with FOLFIRI plus bevacizumab.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e14630-e14630
Author(s):  
Humaid O. Al-Shamsi ◽  
Mahraz Anjum ◽  
Abdulaziz Mohammed Al Farsi ◽  
Hua Shen ◽  
Richard J. Cook ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Risk Factors ◽  
Multivariate Analysis ◽  
Metastatic Colorectal Cancer ◽  
Control Groups ◽  
Single Institution ◽  
Increase Risk ◽  
Treatment Data ◽  
Metastatic Sites ◽  
Colorectal Cancer Patients

e14630 Background: To determine the incidence and risk factors for thrombotic events (TEs) (arterial and venous) in patients with metastatic colorectal cancer (mCRC) who received Bevacizumab and FOLFIRI (Leucovorin, Fluorouracil and Irinotican ) compared to FOLFIRI alone. Methods: Single institution retrospective study of 450 mCRC patients who received either Bevacizumab plus FOLFIRI or FOLFIRI alone between October 2006 and September 2012. Demographics , TE risk factors and treatment data were abstracted from patients records. Multivariate analysis was used to determine factors that contributed to increased TE incidence. Results: 261 mCRC patients received Bevacizumab plus FOLFIRI ( 64.8 % males , mean Body Mass Index (BMI) 26.1 ) compared to 189 control patients who received FOLFIRI alone ( 61.1 % males ,BMI 27). The incidence of TEs was 15 % (arterial 1.8% + venous 13.2%) in the Bevacizumab plus FOLFIRI group compared to 15.8% (arterial 2.1% + venous 13.7%) in the control groups. Multivariate analysis controlled for age, BMI, gender, malignancy, metastatic sites , line of treatment, and risk factors did not suggest a significant increase in risk of TE associated with Bevacizumab (OR=0.83 95% CI: 0.40 - 1.70; p=0.602). No difference in locations of TEs was observed between both groups . The only statistically significant factor for thrombosis in Bevacizumab group was increased BMI (OR=1.05; 95% CI: 1.01- 1.10; p=0.016). Conclusions: Our data suggest that bevacizumab did not significantly increase the rate of thrombosis in patients with mCRC when added to FOLFIRI. To our knowledge this is the first study reporting the rate of TEs (arterial and venous) in this population.Our data suggest that BMI may be a risk factor for increase risk of thrombosis in patients treated with bevacizumab . Clinician should consider risk factors assessment prior to initiating bevacizumab .

Misregulation of the Dependence Receptor DCC and its Upstream lincRNA, LOC100287225, in Colorectal Cancer

2015 ◽  
Vol 103 (1) ◽  
pp. 40-43 ◽  
Author(s):  
Mina Kazemzadeh ◽  
Reza Safaralizadeh ◽  
Mohammad Ali HosseinPour feizi ◽  
Mohammad Hossein Somi ◽  
Behrooz Shokoohi
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Regulation Of Gene Expression ◽  
Cellular Processes ◽  
Qrt Pcr ◽  
Cis Regulation ◽  
Tumor Tissues ◽  
Non Coding Rnas ◽  
Colorectal Cancer Patients ◽  
Dependence Receptor

Background Long non-coding RNAs (lncRNAs), a class of regulatory RNAs, play a major role in various cellular processes. Long intergenic non-coding RNAs (lincRNAs), a subclass of lncRNAs, are involved in the trans- and cis-regulation of gene expression. In the case of cis-regulation, by recruiting chromatin-modifying complexes, lincRNAs influence adjacent gene expression. Methods We used quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR) to evaluate the coexpression of LOC100287225, a lincRNA, and DCC, one of its adjacent genes that is often decreased in colorectal cancer, in pairs of tumor and adjacent tumor-free tissues of 30 colorectal cancer patients. Results The qRT-PCR results revealed the misregulation of these genes during tumorigenesis. Their relative expression levels were significantly lower in tumor tissues than adjacent tumor-free tissues. However, the analysis found no significant correlation between reduced expression of these genes. Conclusions Our study demonstrated the concurrent misregulation of DCC and LOC100287225 in colorectal cancer.

scholarly journals Tissue tRNA‐Derived Fragments (tRFs) as Potential Candidates Correlate with Invasiveness in Colorectal Carcinomas

2020 ◽  
Author(s):  
maryam sahlolbei ◽  
Fahimeh Fattahi ◽  
Somayeh Vafaei ◽  
Rezvan Rajabzadeh ◽  
Zahra Madjd ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Cancer ◽  
Surgical Techniques ◽  
Clinical Pathology ◽  
Predictive Biomarkers ◽  
Tissue Samples ◽  
Protein Coding ◽  
Advanced Therapy ◽  
Invasion Stage ◽  
Non Coding Rnas

Abstract Background Colorectal cancer (CRC), which is one of lethal and invasive cancer with metastasis at the time of diagnosis. Despite, advanced therapy and surgical techniques, Patients with metastases CRC have a poor survival rate. Enhanced predictive biomarkers such as non-coding RNAs (ncRNAs) are needed at the time of diagnosis to better therapies. The tRNA- derived fragments (tRF) are non-protein-coding sequences that probably function as oncogenes or tumor suppressor genes, tRFs produced under physiological or stress conditions from enzymatically cleavage in tRNAs. Methods Documenting the tRNA-derived fragments (tRF) in colorectal cancer and showed that it is significantly down-regulated in colorectal tissue tumors compared to normal tissue samples. Since data distribution was not normal, Mann-Whitney, Kruskal-Wallis, and Spearman correlation coefficient tests were used for analysis. Results Among several tRF, quantitative real-time PCR analyses declared that tRF/miR-1280, tRNA-derived fragment-Asp, tRNA-derived fragment-Val down-regulated in CRC. Notably, its expression was correlated with invasive stage and metastases (p < 0.05). Conclusions This research can elucidate the association between tRFs with the invasion stage and CRC clinical pathology, our results not only expand better understanding about tRNA-derived fragments species in CRC but also highlight the potential usages of tRFs as a promising biomarker in the prognosis of metastatic cancer.

scholarly journals Exosomal Non Coding RNA in LIQUID Biopsies as a Promising Biomarker for Colorectal Cancer

2020 ◽  
Vol 21 (4) ◽  
pp. 1398 ◽  
Author(s):  
Amro Baassiri ◽  
Farah Nassar ◽  
Deborah Mukherji ◽  
Ali Shamseddine ◽  
Rihab Nasr ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Sensitivity And Specificity ◽  
Liquid Biopsy ◽  
Early Stage ◽  
Noncoding Rnas ◽  
Predictive Biomarkers ◽  
Carbohydrate Antigen ◽  
Combination Regimen ◽  
Liquid Biopsies ◽  
Diagnostic Potential

Colorectal cancer (CRC) is one of the most common cancers worldwide, with a high mortality rate, especially in those that are diagnosed in late stages of the disease. The current screening blood-based markers, such as carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9), have low sensitivity and specificity. Meanwhile, other modalities are either expensive or invasive. Therefore, recent research has shifted towards a minimally invasive test, namely, liquid biopsy. Exosomes are favorable molecules sought in blood samples, since they are abundant, stable in circulation, and harbor genetic information and other biomolecules that could serve as biomarkers or even therapeutic targets. Furthermore, exosomal noncoding RNAs, such as miRNAs, lncRNAs, and circRNAs, have demonstrated the diagnostic potential to detect CRC at an early stage with a higher sensitivity and specificity than CEA and CA19-9 alone. Moreover, they have prognostic potential that is TNM stage specific and could serve as predictive biomarkers for the most common chemotherapeutic drug and combination regimen in CRC, which are 5-FU and FOLFOX, respectively. Therefore, in this review, we focus on the role of these exosomal noncoding RNAs as diagnostic, prognostic, and predictive biomarkers. In addition, we discuss the advantages and challenges of exosomes as a liquid biopsy target.

scholarly journals Current Approaches for Predicting a Lack of Response to Anti-EGFR Therapy inKRASWild-Type Patients

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Tze-Kiong Er ◽  
Chih-Chieh Chen ◽  
Luis Bujanda ◽  
Marta Herreros-Villanueva
Keyword(s):  
Colorectal Cancer ◽  
Growth Factor Receptor ◽  
Predictive Biomarkers ◽  
Genetic Determinants ◽  
Secondary Resistance ◽  
Epidermal Growth ◽  
The Right ◽  
Colorectal Cancer Patients ◽  
Selection Of Patients ◽  
Selection Of

Targeting epidermal growth factor receptor (EGFR) has been one of the most effective colorectal cancer strategies. Anti-EGFR antibodies function by binding to the extracellular domain of EGFR, preventing its activation, and ultimately providing clinical benefit.KRASmutations in codons 12 and 13 are recognized prognostic and predictive biomarkers that should be analyzed at the clinic prior to the administration of anti-EGFR therapy. However, still an important fraction ofKRASwild-type patients do not respond to the treatment. The identification of additional genetic determinants of primary or secondary resistance to EGFR targeted therapy for further improving the selection of patients is urgent. Herein, we review the latest published literature highlighting the most important genes that may predict resistance to anti-EGFR monoclonal antibodies in colorectal cancer patients. According to the available findings, the evaluation ofBRAF,NRAS,PIK3CA, andPTENstatus could be the right strategy to select patients who are likely to respond to anti-EGFR therapies. In the future, the combination of those biomarkers will help establish consensus that can be introduced into clinical practice.

scholarly journals Validation of miR-1228-3p as Housekeeping for MicroRNA Analysis in Liquid Biopsies from Colorectal Cancer Patients

Biomolecules ◽  
2019 ◽  
Vol 10 (1) ◽  
pp. 16
Author(s):  
Saray Duran-Sanchon ◽  
Elena Vila-Navarro ◽  
Maria Marcuello ◽  
Juan José Lozano ◽  
Jenifer Muñoz ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Research Field ◽  
Circulating Microrna ◽  
Endogenous Control ◽  
Serum Samples ◽  
Liquid Biopsies ◽  
Circulating Mirna ◽  
Polymerase Chain ◽  
Advanced Adenomas ◽  
Colorectal Cancer Patients

Background: Circulating microRNA (miRNA) analysis is a growing research field. However, it usually requires an endogenous control or housekeeping (HK) in order to normalize expression of specific miRNAs throughout different samples. Unfortunately, no adequate HK for circulating miRNA analysis is still known in the colorectal cancer (CRC) context whereas several have been suggested. Hence, our aims were to validate the previously suggested miR-1228-3p as HK for CRC studies, to compare its suitability with the widely used miR-16-5p, and to evaluate the influence of hemolysis on both miRNAs. Methods: We analyzed by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) the expression of miR-1228-3p, miR-16-5p and the spike-in cel-miR-39 in a set of 297 plasmas (92 CRC, 101 advanced adenomas -AA-, and 100 controls) and 213 serum samples (59 CRC, 74 AA and 80 controls). We also analyzed both miRNAs depending on the hemolysis degree in 7 plasmas and 31 serums. Results: Levels of miR-1228-3p and miR-16-5p did not show significant differences between groups although miR-16-5p exhibited more variability in plasma and serum samples. Importantly, the combination of cel-miR-39 and miR-1228-3p was the most stable one. Moreover, we observed that miR-16-5p was significantly influenced by hemolysis in contrast with miR-1228-3p that exhibited no correlation with this confounding factor in both biofluids. Conclusion: MiR-1228-3p has been validated as an adequate endogenous control for circulating miRNA analysis in CRC and AA liquid biopsies.

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